Summary

Digital clubbing may also occur in isolation (e.g., familial clubbing, as an autosomal-dominant trait).

Definition

Clubbing is described as a bulbous uniform swelling of the soft tissue of the terminal phalanx of a digit with subsequent loss of the normal angle between the nail and nail bed. The first stage of clubbing is a periungual erythema and a softening of the nail bed; this is followed by an increase in the Lovibond angle (the angle between the proximal nail fold and the nail plate). Eventually the depth of the distal phalange increases and the distal interphalangeal joint may become hyperextensible.
[1]Marrie TJ, Brown N. Clubbing of the digits. Am J Med. 2007;120:940-941.
http://www.ncbi.nlm.nih.gov/pubmed/17976417?tool=bestpractice.com

The Schamroth window test can be used to identify or confirm clubbing. If 2 opposing fingers are held back to back against each other, a diamond-shaped space should normally appear between the nail beds and the nails of the 2 fingers. In clubbing, this space (or window) is missing.
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Schamroth window test demonstrating a diamond-shaped window when fingers are not clubbed
Created by BMJ Knowledge Centre [Citation ends].[Figure caption and citation for the preceding image starts]:
Schamroth window test demonstrating lack of window with clubbed fingers
Created by BMJ Knowledge Centre [Citation ends].

Clubbing is usually bilateral, although unilateral clubbing does exist (e.g., axillary artery aneurysm and brachial arteriovenous malformations). It is painless unless associated with underlying conditions such as pulmonary hypertrophic osteoarthropathy. The vast majority of patients are unaware of its presence. However, an understanding of the causation and diseases associated with clubbing alerts the physician to the seriousness of this sign and the need to investigate the patient appropriately.
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Finger clubbing
From the collection of Dr Murlidhar Rajagopalan [Citation ends].[Figure caption and citation for the preceding image starts]:
Pachydermoperiostosis: toe clubbing
From the collection of Dr Murlidhar Rajagopalan [Citation ends].[Figure caption and citation for the preceding image starts]:
Clubbing of nails showing loss of the classic Lovibond angle
From the collection of Dr Murlidhar Rajagopalan [Citation ends].

Pathophysiology

Advances in the study of the pathogenesis have established that vascular endothelial growth factor (VEGF) is key. This platelet-derived factor is stimulated by hypoxia and produced in diverse malignancies and conditions that affect circulation. VEGF induces vascular hyperplasia, edema, and fibroblast or osteoblast proliferation at a peripheral level in the nails. In primary pulmonary conditions such as lung cancer, this is the operative mechanism. When there is extrapulmonary shunting of blood - for example, in cyanotic heart disease - large megakaryocytic fragments gain access to the systemic circulation and affect distal sites such as the nails. Here, these fragments release growth factors, including VEGF.
[1]Marrie TJ, Brown N. Clubbing of the digits. Am J Med. 2007;120:940-941.
http://www.ncbi.nlm.nih.gov/pubmed/17976417?tool=bestpractice.com
[2]Martinez-Lavin M. Exploring the cause of the most ancient clinical sign of medicine: finger clubbing. Semin Arthritis Rheum. 2007;36:380-385.
http://www.ncbi.nlm.nih.gov/pubmed/17276498?tool=bestpractice.com

A neural mechanism involving the vagal system has also been proposed, following the observation that pathology and disease of vagally innervated organs is associated with an increased incidence of clubbing and that clubbing may be reversed following vagotomy. This has been especially noted in cases with hypertrophic osteoarthropathy. However, this hypothesis is now decreasing in popularity.

Platelet derived growth factor (PDGF) may have a role. Platelets release PDGF in the vasculature of the fingertips. PDGF stimulates growth, vascular permeability, and monocyte and neutrophil chemotaxis, and leads to proliferation of vascular smooth muscle cells and fibroblasts, as is seen in clubbing.
[4]Dickinson CJ, Martin JF. Megakaryocytes and platelet clumps as the cause of finger clubbing. Lancet. 1987;2:1434-1435.
http://www.ncbi.nlm.nih.gov/pubmed/2891996?tool=bestpractice.com
In addition, clubbing may be stimulated by local arteriovenous anastomoses provoked by neurocirculatory stimuli. Conditions that have chronic platelet excess (e.g., inflammatory bowel disease) result in peripheral platelet trapping and release of PDGF.
[4]Dickinson CJ, Martin JF. Megakaryocytes and platelet clumps as the cause of finger clubbing. Lancet. 1987;2:1434-1435.
http://www.ncbi.nlm.nih.gov/pubmed/2891996?tool=bestpractice.com

As clubbing is a manifestation of several disorders, no single genetic factor predisposes to clubbing. The heredity of each disorder is distinct. Not all are genetic.